The impact of age, sex, and comorbidities on COVID-19 mortality of hospitalized patients during the SARS-CoV-2 pandemic: data from the multicentric prospective cohort study of the Lean European Open Survey on SARS-CoV-2 (LEOSS).

Purpose: This study aimed to analyse COVID-19-related mortality during the pandemic, stratified by groups at risk of severe COVID-19.

Methods: Patients with COVID-19 between March 2020 and February 2023 were enrolled using the international multicentric Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS). The COVID-19 in-hospital mortality was calculated using a multivariable logistic regression model adjusted for age and sex.

Results: A total of 11,765 patients were included, with an overall mortality rate of 13.1% (N = 1541). Mortality decreased from 14.4% during the wildtype (wt) period to 10.6%, 9.5%, and 6.3% in the alpha (α), delta (δ), and omicron (Ω) periods, respectively. Patients aged 66-75, 76-85, and > 85 years had 11.4-, 19.3-, and 34.7-fold higher mortality odds than patients aged 26-35 years (p < 0.001 in all comparisons). This increase in mortality between younger and older patients decreased with the shift from wt (increase of 39.4%) to Ω (15.5%). The overall adjusted mortality rate in males (18.4%) was higher than in females (10.6%); however, this sex-specific difference levelled off with the shift from wt (m: 18.9%, f: 10.1%) to Ω (m: 5.9%, f: 5.3%). Referring to comorbidities, adjusted mortality increased significantly with the number of comorbidities in patients during the wt but remained stable in patients with Ω-period. Among severely immunosuppressed patients, mortality declined markedly throughout the pandemic (wt vs. Ω: p < 0.001).

Conclusion: Overall mortality decreased during the pandemic, even among severely immunosuppressed patients. Age, sex, and the number of comorbidities were key mortality risk factors, although their impact lessened as the pandemic progressed.